The present invention relates to novel N-substituted [2R,3R(2R',3R'),6R,7S, 8S,9R,10R]-3-(2',3'-dihydroxypent-2'-yl)-7-[(2,6-dideoxy-3-C-methyl-3-0-me thyl-.alpha.-L-ribo-hexopyranosyl)-oxy]-9- [(3,4,6-trideoxy-3-amino-.beta.-D-xylo-hexopyranosyl)-oxy]-2,6,8,10,12-pen tamethyl-4,13-dioxabicyclo[8.2.1]tridec-12-en-5-one compounds with motilin-agonistic properties and to the acid addition salts thereof and to pharmaceutical formulations containing these compounds and to process and intermediates for the preparation of these compounds. The compounds according to the invention are ring-contracted N-demethyl-N-isopropyl derivatives of erythromycin A.
In addition to its antibiotic effects, the antibiotic erythromycin A is known to also have gastrointestinal side effects which are undesired in antibiotics, inter alia a great increase in the contraction activity in the gastrointestinal region with gastric and intestinal cramps, nausea, vomiting and diarrhoea.
There have been several attempts to modify erythromycin A to obtain derivatives in which the antibiotic effect is virtually eliminated but an effect influencing the motility of the gastrointestinal tract is obtained. U.S. Pat. No. 4,920,102 discloses pharmaceutical compositions which contain as gastroprokinetic active substance a ring-contracted erythromycin A derivative or a quaternary salt thereof and which enhance gastric motility by cholinergic mechanisms.